Medullary thyroid carcinoma with double negative calcitonin and CEA: a case report and update of literature review.

BACKGROUND: Medullary thyroid carcinoma is a malignant uncommon and aggressive tumour of the parafollicular C cells. In about 75% of cases it is sporadic while, in case of RET mutation, it is associated to multiple endocrine neoplasia type 2 (25% of cases). The biochemical features of medullary thyroid carcinoma include the production of calcitonin and carcinoembryogenic antigen. The above-mentioned features are useful in the diagnostic process as well as in the follow up and in the prognostication of the disease. Even if calcitonin elevation is strongly associated to MTC, it can also be found increased in many pathological different conditions as pregnancy, lactation, C-cells hyperplasia, autoimmune thyroiditis, end stage renal disease, lung and prostate cancer and several neuroendocrine tumours. Major medullary thyroid tumours are usually connected to high doses of circulating calcitonin, in fact non-secretory variants have hardly been described. CASE PRESENTATION: We herein report the case of a 59 years old male, who had undergone total thyroidectomy for multinodular goiter with negative preoperative calcitonin, showing medullary thyroid carcinoma at definitive pathology. To the best of our knowledge, this is the first case documenting a non-secretory medullary thyroid carcinoma, with double negative markers at the time of diagnosis and at the relapse. CONCLUSION: A Literature review underlining pathological hypothesis, differential diagnosis and alternative and innovative biomarkers to identify non-secretory medullary thyroid carcinoma was carried out.

Calcitonin negative Medullary Thyroid Carcinoma: a challenging diagnosis or a medical dilemma?

BACKGROUND: Medullary thyroid carcinoma is a neuroendocrine tumor belonging form a malignant growth of the thyroid parafollicular C-cells, representing from 1 to 10% of all thyroid cancer. The biochemical activity of medullary thyroid carcinoma includes the production of calcitonin and carcinoembryogenic antigen, which are sensitive tumor markers, facilitating the diagnosis, follow-up and prognostication. The diagnosis is reached through the identification of high basal calcitonin serum level or after pentagastrin stimulation test. Medullary thyroid carcinoma is able to produce other relevant biomarkers as procalcitonin, carcinoembryionic antigen and chromogranin A. In Literature are described few cases of medullary thyroid carcinoma without elevation of serum calcitonin, an extremely rare event. The aim of this study was to analyse the presentation, the main features and therapeutic management of medullary thyroid carcinoma associated with negative serum calcitonin levels. METHODS: Using the PubMed database, a systematic review of the current Literature was carried out, up to February 2018. Finally, nineteen articles met our inclusion criteria and were selected according to the modified Newcastle-Ottawa scale. RESULTS: Fourty-nine patients with definitive pathology confirming medullary thyroid carcinoma and with calcitonin serum level in the normal range were identified (24 female, 24 male and not reported gender in 1 case). Mean age was 51.7 years. Serum calcitonin levels were reported for 20 patients with a mean value of 8.66 pg/mL and a range of 0.8-38 pg/mL. Despite the low or undetectable calcitonin serum level, at immunochemistry in almost the half of the cases reported by the Authors, the tumors presented diffuse or focal positivity for calcitonin and carcinoembryionic antigen, while was reported a chromogranin A positivity in 41 of the 43 tested patients. CONCLUSIONS: Calcitonin negative medullary thyroid carcinoma is an extremely rare pathology. The diagnosis and the surveillance is often challenging and delayed, due to the lack of elevation of serum markers as calcitonin and carcinoembryionic antigen. Further studies are needed, to better define options for management of non secretory medullary thyroid carcinoma and to identify new and reliable biomarkers associated to diagnosis and relapse of this medical dilemma.

Advanced hemostasis in axillary lymph node dissection for locally advanced breast cancer: new technology devices compared in the prevention of seroma formation.

BACKGROUND: Breast cancer is the most frequent neoplasm in women. Axillary lymph nodes dissection represents the treatment of choice in locally advanced breast cancer for prognostic and curative purposes. Seroma formation, an abnormal collection of fluid in the dead space of the axilla, is described in Literature with a wide range of incidence (3-85%). It is a source of significant morbidity and discomfort. The aim of the study is to compare the different haemostasis devices used in breast surgery, investigating the eventual superiority of an instrument among the others in terms of intraoperative and postoperative outcome, especially of seroma formation. METHODS: Clinical cases of female patients undergone axillary lymph nodes dissection for local advanced breast cancer between January 2013 and July 2017 at the Surgery Unit of University of Campania "Luigi Vanvitelli" were retrospectively reviewed. Patients were divided into four groups, according to device utilized during surgery: Electrocautery, Harmonic Scalpel, LigaSure and Thunderbeat. All patients underwent II level axillary lymph nodes dissection associated to radical mastectomy or quadrantectomy. RESULTS: One hundred consecutives patients were enrolled in the study. Intra-operative blood loss resulted statistically significant different (P < 0,01) between the Electrocautery group (94,7 ml) and the Thunderbeat group (57,2 ml), while the Harmonic Scalpel group and the Ligasure group, despite presented a lower amount of blood loss, did not differ significantly. Drainage volume resulted significantly lower (P = 0,002) in the comparison between the Electrocautery group and the Thunderbeat group; the Ligasure group and Harmonic Scapel group showed no difference between them and Electrocautery group. About the seroma formation, the Electrocautery group resulted affected by the highest seroma formation rate (64%). Seroma incidence in Harmonic Scalpel group was 24%, in Ligasure group was 44%, while Thunderbeat group showed the lowest presentation of seroma with 16%. CONCLUSIONS: In patients affected by breast cancer requiring axillary lymphnodes dissection, the use of advanced hemostasis devices is highly desirable. Among the non-traditional tools, Thunderbeat resulted to be superior in terms of reduction of intra-operative blood loss and post-operative drainage output, moreover associated to a substantial reduction of postoperative seroma incidence.

The role of prophylactic central compartment lymph node dissection in elderly patients with differentiated thyroid cancer: a multicentric study.

BACKGROUND: Prophylactic central neck lymph-nodes dissection is still a topic of major debate in Literature. There is a lack of randomized controlled trials proving advantages in its application in terms of overall survival and local recurrence. Due to the recent rapid increase of elderly population, differentiated tumor carcinoma diagnosis increased in patients over 65 years old. The aim of this study was to compare recurrence rate, complications rate and histological features of tumors in elderly population. METHODS: A retrospective study was carried out collecting data from 371 patients with differentiated thyroid cancer without clinical evidence of lymph-nodes involvement in three Italian referral centers from 2005 to 2015. All patients were aged ≥ 65 years and were divided in two groups based on the performed surgery (total thyroidectomy alone or associated with central lymph-nodes dissection). Moreover, patients were stratified according to the age between 65 and 74 years old and over 75 years old. RESULTS: Total thyroidectomy alone was performed in 184 patients (group A) and total thyroidectomy with prophylactic central neck dissection was performed in 187 cases (group B). There was a statistically significant difference in complications between the groups in terms of neck hematoma (0.5% group A vs 3.7% group B), temporary hypoparathyroidism (11.4% group A vs 21.4% group B), and temporary unilateral recurrent nerve injury (1.5% group A vs 6.4% group B). Lymph nodes recurrence rate was 9.2% in group A and 8.5% in group B, with no statistically significant difference. There was a statistically significant difference in patients over 75 years old in terms of temporary hypoparathyroidism (24% group A vs 11% group B), permanent hypoparathyroidism (2,7% group A vs 0,3% group B) and recurrent nerve injury (9,5% group A vs 2% group B). CONCLUSIONS: The role of prophylactic central neck dissection is still controversial, especially in elderly patients, and an aggressive surgical approach should be carefully evaluated. The Authors reported a similar low recurrence rate between total thyroidectomy and total thyroidectomy associated with prophylactic central neck dissection, with increased postoperative complications in the lymphadenectomy group and in patients over 75 years old, advocating a tailored surgical approach in elderly population.

Single center experience with laparoscopic adrenalectomy on a large clinical series.

BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard technique for the treatment of benign small and medium size adrenal masses (<6 cm), due to low morbidity rate, short hospitalization and patient rapid recovery. The aim of our study is to analyse the feasibility and efficiency of this surgical approach in a broad spectrum of adrenal gland pathologies. METHODS: Pre-operative, intra-operative and post-operative data from 126 patients undergone laparoscopic adrenalectomy between January 2003 and December 2015 were retrospectively collected and reviewed. Diagnosis was obtained on the basis of clinical examination, laboratory values and imaging techniques. Doxazosin was preoperatively administered in case of pheochromocytoma while spironolactone and potassium were employed to treat Conn's disease. Laparoscopic adrenalectomies were all performed by the same surgeon (CG). First 30 procedures were considered as learning curve adrenalectomies. RESULTS: One hundred twenty-six patients were included in the study. Functioning tumors were diagnosed in 84 patients, 27 patients were affected by pheochromocytomas, 29 by Conn's disease, 28 by Cushing disease. Surgery mean operative time was 137.33 min (range 100-180) during the learning curve adrenalectomies and 96.5 min (range 75-110) in subsequent procedures. Mean blood loss was respectively 160.2 ml (range 60-280) and 90.5 ml (range 50-200) in the first 30 procedures and the subsequent ones. Only one conversion to open surgery occurred. No post-operative major complications were observed, while minor complications occurred in 8 patients (0,79%). In 83 out of 84 functioning neoplasms, laparoscopic adrenalectomy was effective in normalization of endocrine profile. CONCLUSIONS: Laparoscopic adrenalectomy is a safe and feasible procedure, even for functioning masses and pheochromocytomas. A multidisciplinary team including endocrinologists, endocrine surgeons and anaesthesiologists, is recommended in the management of adrenal pathology, and adrenal surgery should be performed in referral high volume centers. A thirty-procedures learning curve is recommended to improve surgical outcomes.